Abstract
Background: Rheumatoid arthritis (RA) is a multi-factor disease with a key role of genetic component in its genesis. Development of osteoporosis and articular destruction is attributed with overexpression of pro-infl ammatory cytokines and reduced production of anti-infl ammatory ones. In this work probable associations of IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-18 and TNFα alleles with rheumatoid arthritis were studied among Russian ethnic group. Methods: A total of 69 Russian ethnical group patients with RA (cases) and 133 healthy control individuals (controls) were genotyped for variants in 8 cytokines genes (IFN-γ, IL-1α, IL-1β, IL-4,IL-6, IL-10, IL-18 and TNFα). Individual genotype and haplotype frequencies were compared between cases and controls. Odd ratios were calculated with asymptotic 95% confi dence intervals and P values less than 0.05 were considered statistically signifi cant. Results: The distribution of studied alleles of cytokine genes in Russian population is similar to other European populations. Genotype, allele and haplotype frequencies were equally distributed between RA cases and controls for IFN-γ (rs2430561), IL-1α (rs1800587), (rs17561), IL-1β (rs1143627), (rs16944), (rs1143634), IL-10 (rs1800871), IL- 18 (rs1946518) and TNFα (rs361525). Meanwhile, signifi cant associations (р<0.05) were found between RA cases and controls for IL-4 (rs2243250) T/T, IL-6 (rs1800795) G/G, IL-10 (rs1800872) A/A, IL-10 (rs1800896) G/A, IL-18 (rs187238) G/C and TNFα (rs1800629) G/A. Conclusions: These results indicate that common variants of the IL-4, IL-6, IL-10, IL-18 and TNFα may signifi cantly contribute to RA susceptibility.
Highlights
Rheumatoid arthritis (RA) is a multi-factor disease with a key role of genetic component in its genesis
We characterised frequencies of the listed above polymorphisms for the group of patients with RA and healthy individuals of Russian ethnic group (Table 2)
10), C-607A (IL-18), G-238A (TNF ). These results corresponds to Tulusso et al, who showed no associations between RA and T-31C, C-511T (IL-1 ) [20]
Summary
Rheumatoid arthritis (RA) is a multi-factor disease with a key role of genetic component in its genesis. Development of osteoporosis and articular destruction is attributed with overexpression of pro-inflammatory cytokines and reduced production of anti-inflammatory ones. In this work probable associations of IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-18 and TNFα alleles with rheumatoid arthritis were studied among Russian ethnic group. Genetic component of A susceptibility was established by data from twin and family studies [2]. SNPs of regulator sites or introns influence on transcription by transformation of ranscriptional factor binding sites or enhancer structures. Such positive and negative regulation of cytokine expression plays an important role in development of local inflammations, and is one of RA etiological factors.
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